期刊
CELL DEATH & DISEASE
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2017.129
关键词
-
类别
资金
- Ministry of Science and Technology of China [2015DFG32200]
- National Natural Science Foundation of China [81401844, 81572123]
- Science and Technology Commission of Shanghai [15411951100, 16ZR1441700, 16430723500]
- Shanghai Municipal Commission of Health and Family Planning [2013ZYJB0501]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine [20161314]
The incomplete understanding of aberrant neovascularization, which contributes to osteoarthritis suggests that additional modulators have yet to be identified. Our objective was to identify the role of Leucine-rich-alpha-2-glycoprotein1 (LRG1), a new regulator of pathogenic angiogenesis, in osteoarthritis progression and to develop effective treatment strategies. In this study, immunohistochemistry showed that LRG1 was increased in the subchondral bone and articular cartilage in anterior cruciate ligament transection (ACLT) mice. Further studies were focused on the role of LRG1 in osteoarthritis. Results showed that LRG1 promoted angiogenesis and mesenchymal stem cells (MSC) migration, which contribute to aberrant bone formation in the subchondral bone. Moreover, tumor necrosis factor-alpha (TNF-alpha), not interleukin-1 beta (IL-1 beta), IL-6 or IL-17, induced the LRG1 expression in human umbilical vein endothelial cells and this effect was inhibited by p38 mitogen-activated protein kinase or NF-kappa B inhibitor. Notably, inhibition of TNF-alpha and LRG1 activity by Lenalidomide, an inhibitor of TNF-alpha production, in ACLT mice attenuated degeneration of osteoarthritis articular cartilage. This study shows that TNF-alpha is the predominant proinflammatory cytokine that induces the secretion of LRG1. LRG1 contributes to angiogenesis-coupled de novo bone formation by increasing angiogenesis and recruiting MSCs in the subchondral bone of osteoarthritis joints. Inhibition of TNF-alpha and LRG1 by Lenalidomide could be a potential therapeutic approach.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据